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Atezolizumab results show benefit for selected NSCLC patients

New England Journal of Medicine
Reuters Health - 30/09/2020 - In a small group of selected patients with metastatic non-small-cell lung cancer, first-line treatment with atezolizumab extends median overall survival by just over 7 months, or 41%, compared to platinum-based chemotherapy, according to interim results of the IMpower110 study funded by Roche and Genentech.

The findings, published in The New England Journal of Medicine, only apply to patients with metastatic NSCLC who had wild-type epidermal growth factor receptors (EGFR) or anaplastic lymphoma kinase (ALK) mutations and had the highest expression of programmed death ligand 1 (PD-L1).

Of the more than 1.5 million people diagnosed with lung cancer each year, probably 20% to 30% of them could be candidates for the treatment under the terms of the study, lead author Dr. Roy Herbst, chief of medical oncology at the Yale University Cancer Center, told Reuters Health in a telephone interview.

Out of the 572 volunteers enrolled in IMpower10, 205 fell into that category. None had previously received chemotherapy for their stage IV non-squamous or squamous lung cancer tumors.

The results prompted the U.S. Food and Drug Administration (FDA) to approve the drug on May 18 for first-line therapy for such patients.

The drug, sold under the brand name Tecentriq, is a monoclonal antibody that acts as a "checkpoint inhibitor." It targets the PD-L1 protein on the surface of tumor cells that prevents the T cells of the immune system from attacking the tumor. With the PD-L1 protein neutralized, the T cells can do their job.

A similar drug for this group of patients, Merck's Keytruda (lambrolizumab), was approved by the FDA five years ago.

"The drugs look very equivalent," said Dr. Herbst, and that may affect whether doctors start using Tecentriq as first-line treatment.

The overall survival was 13.1 months for the volunteers who received conventional chemotherapy and 20.2 months with atezolizumab (P=0.01).

The median overall survival for patients with wild-type tumors who had any degree of PD-L1 expression was longer with atezolizumab, but not significantly so.

Progression-free survival in the 205-patient group with the highest PD-L1 expression was 8.1 months with atezolizumab and 5.0 months with conventional chemotherapy.

The 12-month overall survival rate was 64.9% with the drug and 50.6% with chemotherapy, with a median follow-up of 15.7 months.

Fatigue and weakness were the most common side effects.

The rates of grade 3 or 4 side effects also favored atezolizumab in all patients. They were seen in 30.1% of patients who received the drug versus 52.5% in the control group.

The companies helped collect, analyze and interpret the data from the 144 centers in 19 countries.

Dr. Herbst said that when he first started treating lung cancer, "nobody wanted to work in the field. The median time you survived was a couple of months -- maybe 6 months. If you got to a year, it was amazing. Now we're seeing people go on for years with these drugs."

"Now we have to build on this progress by combining them with other drugs" in hopes of getting even better outcomes, he said.

By Gene Emery

SOURCE: https://bit.ly/2Gea5IE The New England Journal of Medicine, online September 30, 2020.

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